There are many instances in which a neurosurgeon or other clinician would wish to deliver a therapeutic or diagnostic agent into the brain of a patient, for example, for the treatment of primary malignant brain tumors. One type of such tumor, glioblastoma multiforme, is a lethal malignancy of the central nervous system that has proven stubbornly resistant to the development of any form of satisfactory therapy that can either halt the advance of the disease, reverse it, or cure it. Anticancer therapies that are often efficacious in other regions of the body, such as chemotherapies, are largely ineffective against diffuse neoplasms in the brain in part because of the presence of the blood-brain barrier. Even in the case where the blood-brain barrier is “leaky” within the tumor bed of a glioblastoma multiforme, regional delivery into the peritumoral region (which often harbors invading cells) in which the chemotherapies, gene therapies, and other agents are targeted is hampered by the intact blood-brain barrier in that region, thus making such approaches unworkable. A means of circumventing such delivery problems is offered by the positive pressure infusion of agents directly into the bulk brain tissues, as taught by several workers, examples of which are: U.S. Pat. No. 5,720,720 to Laske, et al., U.S. Pat. No. 6,026,316 to Kucharczyk, et al., and U.S. Pat. No. 6,272,370 to Gillies, et al., of which all of the disclosures are hereby incorporated by reference herein in their entirety. The resulting convection-enhanced flow of infusates through the interstitial space of the brain can provide for regional volumes of distribution of therapeutic agents without the need to have large-molecular weight species traverse the blood-brain barrier. Often, special neurocatheters optimized for this approach to drug delivery are needed to maximize the utility of such therapies. This general approach to intraparenchymal therapies also applies to the delivery of autologous stem cells into the brain for the treatment of neurodegenerative disorders, and for the infusion protocols for the assessment and treatment of traumatic brain injury. Moreover, positive pressure infusion of therapeutic agents and diagnostic into other parts or ducts of the body, including the vasculature, is also practiced routinely within the field of medicine.
Specialized multi-lumen neurocatheter systems have been disclosed by Kucharczyk et al. in U.S. Pat. Nos. 6,599,274 and 6,626,902, of which both of the disclosures are hereby incorporated by reference herein in their entirety. Coaxial catheters for the delivery of cells into the brain have been disclosed by Kucharczyk et al. in U.S. Pat. No. 6,599,274. Several clinical and pre-clinical applications of various types of neurocatheters are discussed in the following publications: Chen, Z.-J., et al., “Intraparenchymal Drug Delivery via Positive Pressure Infusion: Experimental and Modeling Studies of Poroelasticity in Brain Phantom Gels,” IEEE Transactions on Biomedical Engineering, 49 (2), 85-96, (February 2002), and Broaddus, W. C., et al., “Advances in Image-Guided Delivery of Drug and Cell Therapies into the Central Nervous System,” Neuroimaging Clinics of North America, 11 (4), 727-735, (November 2001), of which all of the disclosures are hereby incorporated by reference herein in their entirety.
One limitation of the art is that none of the catheters that have been developed to date, nor those foreseen in the literature but not yet implemented, have been optimized in design for the complete elimination of reflux of the infused agent along the catheter insertion track or within the device structure (particularly if a multi-lumen system is used). The elimination of such reflux would be a desirable feature, especially in instances where the infusate might consist of highly specialized and difficult to obtain agents such as certain kinds of antisense constructs (see Broaddus, W. C., et al., “Strategies for the Design and Delivery of Antisense Oligonucleotide in Central Nervous System,” Methods in Enzymology: Antisense Technology, Part. B: Applications, 314, 121-135 (2000), which disclosures is hereby incorporated by reference herein in its entirety), but is generally desirable for the optimal delivery of any type of diagnostic or therapeutic agent.
A second limitation of the existing art is that the various types of multi-lumen implantable devices fail to include a suitable flush line to void the internal components of the catheter of any residual amounts of a therapeutic (or other) agent that might remain in them after an initial use, but which should best be removed prior to an additional use, as may be performed with a multi-functional catheter, such as those disclosed in U.S. Pat. No. 6,026,316 to Kucharczyk; and U.S. Pat. No. 6,626,902 to Kucharczyk et al., which are incorporated herein by reference in their entirety.
A third limitation of the art is that the existing multi-lumen catheter designs do not allow simultaneous escape of trapped air and sealing against inter-tube leakage when an inner lumen is inserted into an outer lumen of such a device.
A fourth limitation of the existing art is that the intra-tube flow dividers inside the inner tube of multi-lumen devices seal at the end of the catheter in such a way that there cannot be communication between what could otherwise function as infusion and flushing channels.
A fifth limitation of the existing art is that many types of existing multi-lumen, multi-port hole catheters require the use of an internally inflatable balloon to either enable the drug delivery or port hole selection process. Examples of such devices and associated methods are those taught by Baran et al. in U.S. Pat. No. 4,423,725, Schweich et al. in U.S. Pat. No. 5,716,340 and Lary in U.S. Pat. No. 6,506,180, of which all of the disclosures are hereby incorporated by reference herein in their entirety. A general discussion of clinical applications of multi-port hole catheters for imaging of intravascular gene therapy has been presented by Xiaoming Yang, “Imaging of Vascular Gene Therapy,” Radiology, 228 (1), 36-49 (July 2003), of which the disclosure is hereby incorporated by reference herein in its entirety. Other publications that are incorporated by reference herein in their entirety including the following: Broaddus, W. C., Gillies, G. T., and Kucharczyk, J., “Image-Guided Intraparenchymal Drug and Cell Therapy,” in Latchaw, R. E., Kucharczyk, J., and Moseley, M. E., eds., Imaging of the Nervous System: Diagnostic and Therapeutic Applications, Vol. 2 (Elsevier-Mosby, Philadelphia, 2005), Chap. 72, pp. 1467-1476; Chiocca, E. A., Broaddus, W. C., Gillies, G. T., Visted, T., and Lamfers, M. L. M., “Neurosurgical Delivery of Chemotherapeutics, Targeted Toxins, Genetic and Viral Therapies in Neuro-Oncology,” Journal of Neuro-Oncology, 69, 101-117, (2004); Gillies, G. T., Smith, J. H., and Humphrey, J. A. C., “Positive Pressure Infusion of Therapeutic Agents into Brain Tissues: Mathematical and Experimental Simulations,” in Yamaguchi, T., ed., Frontiers of Medical Informatics: Proceedings of the 4th International Symposium on Future Medical Engineering Based on Bio-Nanotechnology (21st Century COE Program), (Tohoku University, Sendai, Japan, 2004), pp. 7-12; and Bauman, M. A., Gillies, G. T., Raghavan, R., Brady, M. L., and Pedain, C., “Physical Characterization of Neurocatheter Performance in a Brain Phantom Gelatin with Nanoscale Porosity: Stead-State and Oscillatory Flows,” Nanotechnology, 15, 92-97, (2004).
None of the multi-lumen intraparenchymal therapy delivery devices existing in the art traverse these limitations, nor does the prior art teach or suggest means, techniques and systems for improving the designs of them such that these limitations would not prevent successful diagnostic and therapeutic protocols from being carried out.
Significant and potentially useful advances in the treatment of glioblastoma multiforme, traumatic brain injury, neurodegenerative disorders and many other neurological and neurosurgical indications could be realized if alternatives to the prior art were able to demonstrate safety and efficacy via improvement of the catheter systems used for therapy delivery. The various embodiments of the present invention disclose a means, technique and system for attempting to reach this goal by implementation of a novel set of catheter structures, functions and means that traverse the limitations of the existing art discussed above and elsewhere.